February 27, 2007

Taking back the FDA

Boston Globe

IT'S TIME to take the Food and Drug Administration back from the drug companies. Before a prescription drug can be sold, the manufacturer must conduct clinical trials to prove to the FDA that the drug is safe and effective. Without that, doctors have no way of knowing how good or bad a drug is. Just trying it out would be ...

Marcia Angell

February 26, 2007

Taking back the FDA
By Marcia Angell February 26, 2007

IT'S TIME to take the Food and Drug Administration back from the drug companies.

Before a prescription drug can be sold, the manufacturer must conduct clinical trials to prove to the FDA that the drug is safe and effective. Without that, doctors have no way of knowing how good or bad a drug is. Just trying it out would be not only risky, but unreliable, since individual experience can be misleading. The scrutiny that this agency exists to provide is vital to our health.

But in 1992, Congress put the fox in the chicken coop. It passed the Prescription Drug User Fee Act, which authorizes drug companies to pay "user fees" to the FDA for each brand-name drug considered for approval. Nearly all of the money generated by these fees has been earmarked to speed up the approval process.

In effect, the user fee act put the FDA on the payroll of the industry it regulates. Last year, the fees came to about $300 million, which the companies recoup many times over by getting their drugs to market faster.

But while it's a small investment for drug companies, it's a lot of money for the agency, and it has drastically changed the way it operates -- creating a disproportionate emphasis on approving brand-name drugs in a hurry. Consequently, the part of the agency that reviews new drugs gets more than half its money from user fees, and it has grown rapidly. Meanwhile, the parts that monitor safety, ensure manufacturing standards, and check ads for accuracy have languished or even shrunk.

Most tellingly, the office that approves generic drugs is so small that approval time for generics is twice as long as for brand-name drugs. There is now a backlog of more than 800 generics. That delay is worth billions of dollars to the drug companies whose high prices depend on not having generic competition.

As part of the emphasis on speed, the FDA often approves brand-name drugs on the basis of less evidence than in the past. In these cases, approval may be contingent on companies conducting further safety studies after the drugs are on the market. But the companies usually don't honor that commitment. Of the roughly 1,200 such studies outstanding -- some for years -- over 70 percent haven't been started.

The FDA is strangely silent about this inexcusable dereliction. When questioned, it weakly protests that it doesn't have the authority to compel the research. In fact, it has enormous leverage, since it can withdraw drugs from the market.

The FDA also refuses to release unfavorable research results in its possession without the sponsoring company's permission. Here again, it contends not to have the authority to do so, but providing evidence of side-effects or negative results would seem to be an integral part of its job. It's no wonder that serious safety concerns about drugs such as Vioxx, Paxil, and Zyprexa have emerged very late in the day -- years after they were in widespread use.

The agency's coziness with industry is underscored by the composition of its 18 advisory committees -- outside experts who help evaluate drugs.

Incredibly, many of these advisers work as consultants for drug companies. Although they are supposed to recuse themselves if there is a direct conflict of interest, the FDA regularly grants exemptions from that requirement. Of the six members of the advisory committee that in 1999 recommended approving Vioxx -- the arthritis drug pulled from the market in 2004 because it caused heart attacks -- four had received waivers from the conflict-of-interest rule.

The FDA now behaves as though the pharmaceutical industry is its user, not the public.
Fortunately, the user fee law is subject to renewal every five years, and this is one of those years.

Congress should let the law die this time around and substitute its own support -- which ought to be increased. Other reforms recently proposed, such as administratively separating drug approval from safety surveillance, will not mean much as long as this law is in effect.

At $300 million to $400 million a year, the equivalent of about a day in Iraq, Congress can easily afford to buy this vital agency back for the public, and it should.

Dr. Marcia Angell, a senior lecturer at Harvard Medical School, is a guest columnist.
© Copyright 2007 Globe Newspaper Company.

February 22, 2007


Some Anti-psychotic Drugs Stimulate Appetite, Lead to Weight Gain

By Rose Hoban Chapel Hill, NC
20 February 2007
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About a decade ago, drug companies introduced new medications to treat serious mental illnesses such as schizophrenia and mania. The drugs, called atypical anti-psychotics, had fewer serious side effects than older medications, which caused lethargy and facial tics. But these new drugs tend to cause people taking them to gain
Dr. Solomon Snyderweight - an astronomical amount of weight, according to Solomon Snyder. "For instance, a 63-kilo patient can end up weighing 108 kilos after only a period of a few months on the drug," he says.
The neuroscience researcher from the Johns Hopkins University in Baltimore, Maryland, wanted to find out why atypical anti-psychotics caused so much weight gain. So he exposed the brains of mice to the drugs and measured their effect on enzymes in a part of brain that controls appetite.
He ended up focusing on an enzyme called AMP kinase, which is known to regulate the desire for food. "We found that these drugs very potently stimulated this enzyme, which would explain why they cause an increase in appetite." Armed with this knowledge, Snyder explains, drug companies could work to alter the chemistry of atypical anti-psychotics so they don't have these effects on brain enzymes. He points to Zyprexa, the most effective and most widely used drug in this class. "Were this drug being developed today, it would be very easy for the drug company to custom design the drug."
Atypical anti-psychotics are widely used throughout the United States, Europe and Japan. Snyder's research is being published in the Proceedings of the National Academy of Sciences.

NEWS MEDIA UPDATE · SECOND CIRCUIT · Prior Restraints · Feb. 22, 2007
Wiki Web site no longer enjoined in Eli Lilly case
Other parties are still under an injunction to return confidential documents.
Feb. 22, 2007 · An anonymous Web poster who challenged a judge's order enjoining a wiki – a Web site that allows users to edit the content of a site – from posting a link to confidential documents about Eli Lilly's controversial drug Zyprexa has won his court battle.
A federal judge in New York ruled Feb. 13 that a previously issued preliminary injunction will no longer apply to the enjoined Web site.
However, U.S. District Judge Jack B. Weinstein ruled that the injunction still holds to some other parties, who must return and refrain from disseminating the documents.
Eli Lilly is being sued over Zyprexa in both federal and state courts by patients who say the pharmaceutical company deliberately downplayed the side effects of the drug, which is used to treat schizophrenia and bipolar disorder. The documents at the center of the controversy are materials about Zyprexa that Lilly submitted under seal during the discovery process.
Plaintiff's expert David Egilman had the documents, but was subject to a protective order to keep the documents confidential.
In his opinion, the judge accused New York Times reporter Alex Berenson of conspiring with Egilman and another attorney, James Gottstein, to obtain the documents. Gottstein got involved in a separate case in which he subpoenaed information about Zyprexa from Egilman, then sent copies to Berenson and more than a dozen others, including congressional staffers and mental health activists.
Times attorney George Freeman said in a statement that Weinstein's opinion "vastly overstates Alex's role in the release of the documents."
The Times published articles using the information contained in the confidential documents. Others posted the documents online and e-mailed the link to others. In response, Lilly asked the court for an injunction.
The court issued a preliminary injunction ordering most of the people who had received the documents directly from Gottstein to refrain from disseminating them, remove posted documents, and tell others to whom they had given the documents to do the same.
Lilly did not pursue an injunction against the Times or Berenson.
Web sites that posted or linked to the documents but did not receive them directly from Gottstein were also enjoined. In a Jan. 4 injunction, Weinstein wrote, "This temporary mandatory injunction further requires the removal of any such documents posted at any website."
The court specifically mentioned the wiki Web site zyprexa.pbwiki.com. An anonymous poster who uses the Web site, known in court papers as "John Doe," challenged the judge's order.
In the Feb. 13 permanent injunction, the judge lifted the injunction on the site zyprexa.pbwiki.com as well as other Web sites.
"Mindful of the role of the internet as a major modern tool of free speech, in the exercise of discretion the court refrains from permanently enjoining websites based on the insubstantial evidence of risk of irreparable harm," the judge wrote. "Restrictions on speech, even in the context of content neutrality, should be avoided if not essential to promoting an important government interest."
Fred von Lohmann, an attorney from the Electronic Frontier Foundation who represented John Doe, said in a press release, "This ruling makes it clear that Eli Lilly cannot invoke any court orders in its futile efforts to censor these documents off the Internet."
However, other parties are still enjoined in the permanent injunction. The judge ordered them to return all copies they have of the documents and prohibited further distribution of the documents. This means that they will not be able to post the documents to Web sites.
Most of the parties enjoined in the permanent injunction received the information firsthand from Gottstein. But at least one of them, David Oaks, received the information third hand.
The judge reasoned that the injunction was not a violation of the First Amendment, arguing that the documents were acquired unlawfully through the discovery process.
The judge distinguished the Zyprexa case from the noteworthy 1996 case Procter & Gamble v. Bankers Trust.
In Procter & Gamble, the Sixth Circuit held that an injunction prohibiting Business Week from publishing litigation filings that had been improperly sealed was unconstitutional.
The Zyprexa case is different, the judge opined, because the documents were discovery documents rather than litigation filings; the documents were never unsealed, unlike those in the Procter & Gamble case; and the enjoined parties are not members of the media.
Von Lohmann disagreed with the judge's interpretation of Procter & Gamble, arguing that the final injunction constituted an unconstitutional prior restraint.
"This is the first occasion to my knowledge where the court has granted a prior restraint against truthful information on a matter of public concern where the enjoined individuals were not involved in misappropriating the material in question," von Lohmann said.
(Zyprexa Litigation, Doe's Counsel: Fred von Lohmann, Electronic Frontier Foundation, San Francisco) -- CS
Related stories:
Times reporter refuses judge’s 'invitation' to testify (02/07/2007)
Judge's order preventing posting of documents challenged (01/19/2007)
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